Lessons learned from the DIG trial.

The Digitalis Investigation Group (DIG) trial was the first large simple trial conducted by the National Heart, Lung, and Blood Institute in conjunction with the Department of Veterans Affairs. A large simple trial is a major undertaking. Simplification at the sites requires careful planning and discipline. Lessons learned from the DIG trial were: (1) keep a large simple trial very simple and keep all study procedures very simple; (2) ancillary studies are important and can complement a large simple trial but require careful advanced planning; (3) anticipate special needs when shipping study drugs internationally; (4) regional coordinating centers can be very useful; (5) recruit as many capable sites as possible; (6) provide research-inexperienced sites/investigators with extra help to obtain federalwide assurance statements from the Office for Human Research Protections and institutional review board approvals; (7) adequately reimburse sites for the work completed; (8) maintain investigator enthusiasm; (9) monitor the slow performers and sites with numerous personnel changes; (10) choose an endpoint that is easy to ascertain; (11) keep the trial simple for participants; and (12) plan early for closeout and for activities between the end of the trial and publication of results.